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2017 Cardiovascular Research Day Abstract Book

43 Intracoronary Versus

43 Intracoronary Versus Intravenous Adenosine-Induced Maximal Hyperemia for Fractional Flow Reserve Measurement: A Systematic Review and Meta-Analysis Mohamed El-Helw, MD 1 • Mohamed Abo-Aly, MD 1 • Georges Lolay, MD 1 • Christopher Adams, MD 1 • Ahmed El-Sharaawy, MD 1 • Ahmed Abdel-Latif, MD, PhD 1 • Khaled Ziada, MD 1 1Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky Postdoc Background: Measurement of fractional flow reserve (FFR) is considered the gold standard technique for the invasive hemodynamic assessment of borderline coronary artery stenosis. Currently, intravenous (IV) adenosine is the recommended approach; however intracoronary (IC) administration is widely used due to its convenience and lower cost. The correlation between IV and IC administration to assess coronary blood flow is not well studied. Objective: This systematic review and meta-analysis is conducted to review the available literature that compared FFR measurements using bolus IC vs. standard continuous IV of adenosine infusion for detection of significant coronary artery stenosis. Methods: We systematically searched MEDLINE, EMBASE, Google scholar and the Cochrane Central Register of Controlled Trials databases. We reviewed data pertaining to the used adenosine doses, side effects of each method of administration and FFR values. We performed statistical analyses examining the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and odds ratio in studies comparing bolus IC adenosine and continues IV adenosine infusion using random effects modelling. Results: We identified 8 studies addressing the primary review question. Compared to standard IV adenosine infusion, the overall sensitivity of IC adenosine is 0.843 (95% C.I. 0.701-0.925, P

44 Recapitulating In Vivo Fibroblast Differentiation Using a Hydrogel Cell Culture System Demetria Fischesser 1 • Onur Kanisicak, PhD 1 • Mario Perera 2 • Neil Ayres, PhD 2 • Jeff D Molkentin, PhD 1 1Molecular Cardiovascular Biology, Cincinnati Children's Hospital • 2 Chemistry, University of Cincinnati Graduate Student Cardiac fibroblasts are resident interstitial cells known to maintain the extracellular matrix (ECM) under normal physiological conditions through the secretion of collagens and other adherent proteins. During injury, these fibroblasts take on an activated, contractile state and deposit additional ECM proteins to contribute to scar formation. While this response is initially beneficial to prevent rupture and further injury, continuous scar development leads to fibrosis, pathological ventricular remodeling and dysfunction, and eventual organ failure. Though much has already been discovered about the importance of fibroblasts during development and injury response, there are still many aspects of their functions that remain unclear. In order to decipher these fibroblast functions, many in vitro systems have been used to easily manipulate fibroblasts while attempting to mimic in vivo conditions. However, most of these systems have used plastic or gelatin-coated plastic as the surface medium. These have proven to be much stiffer than physiological tissue and provide a static system inhospitable to the dynamic changes of the activating fibroblast. In order to mimic an adaptable in vivo environment for fibroblast culture, we have developed a new hydrogel technology to understand fibroblast behavior and differentiation. This technology utilizes gelatin norbornene and a thiol conjugated to a Reversible Addition-Fragmentation Chain Transfer (RAFT) polymer which can dynamically mimic the stiffness of both healthy and fibrotic tissue, thus allowing for seamless modeling of injury and disease in various tissues. Through morphology and differentiation studies, we have found that there is a significant difference between fibroblasts plated on plastic versus softer hydrogels which mimic in vivo conditions. Fibroblasts plated on plastic and stiffer surfaces become very large and flat, and express markers of differentiation, such as alpha-Smooth Muscle Actin (αSMA), within days of plating. On softer hydrogels, however, the fibroblasts remain small and eventually develop long stellate appendages. They produce αSMA much more slowly and at a much less robust level than on stiffer surfaces. The morphology and differentiation pattern seen on softer hydrogels is highly comparable to fibroblasts observed in vivo. We will use these initial findings to better understand the activation and differentiation of fibroblasts and how, in injury, they first inhibit tissue damage and later enhance it. In the future, we plan to manipulate this hydrogel system to intentionally change the stiffness of the surface on which fibroblasts have already been plated to determine if we can mimic disease states as well as reverse the fibroblast activation phenotype seen previously. 60

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